
The invention relates to an apparatus and non-invasive methods to assess autonomic nervous system (ANS) function. By simultaneous recording of electrophysiological and other physiological signals, a complete indication of ANS function can be obtained in just one diagnostic test instead of numerous separate tests.
The autonomic nervous system (ANS) is concerned with the regulation of smooth muscle, cardiac muscle and every other visceral organ in the body. The autonomic nervous system is not directly accessible to voluntary control. Instead, it operates in an automatic fashion on the basis of autonomic reflexes and central control. One of its major functions is the maintenance of homeostasis within the body. The ANS further plays an adaptive role in the interaction of the organism with its surroundings. The ANS has two functionally and anatomically distinct divisions: the sympathetic part and the parasympathetic part.
In many diseases the sympathetic and the parasympathetic parts of the ANS are affected leading to autonomic dysfunction. The evaluation of the presence of ANS disorders requires in interpretation of numerous laboratory tests like blood pressure measurements, heart-rate and respiration-rate recordings, evaluation of the endocrine system and tilt table tests etc. In our prior U.S. Pat. No. 5522386 we disclose a new polygraphical method called electroautonomography (EAG), which can be used to determine the central and/or peripheral ANS function including the autonomic innervation and control of major organ systems as well as of local ANS function. The method is based on the polygraphical recording of skin potentials or electrodermal activity and is called electrovegetography. The electrovegetograph as described in our previous art is based on a sensitive (AC or DC) amplifier means specifically capable of registering skin potentials. Generally skin potentials are recorded with an AC amplifier in combination with the filter settings within the following band pass 0.1-40 Hz. A typical skin potential registration contains skin potential frequencies approximately between 0.033 and 0.33 Hz and amplitudes that can range between 0.05-2.0 mV. These values are based on rest recordings before the occurrence of habituation. The initial high amplitudes are thought to be a result of the subject""s emotional status. After several minutes the amplitudes decrease to a level that reflect ANS activity. Upon stimulation the amplitude of the skin potentials may raise up to 5 mV. The extent of the reaction to the stimulus is thought to be largely depended on the subject""s ANS activity.
The determination of the so called autonomic nerve conduction velocity or NCV can be more accurately performed using the fast waves obtained from skin potential recordings, because these fast waves display a sharp onset of an evoked response, whereas the xe2x80x9cnormal skin potentialsxe2x80x9d do not always display a sharp onset and especially not after the occurrence of habituation. This characteristic of xe2x80x9cnormalxe2x80x9d skin potentials complicates the calculation of the autonomic nerve conduction velocity, resulting in wrong calculations of the NCV. In practice this may mean for instance that a beginning neuropathy is not detected, whereas the calculation of the NCV using the fast waves is much less susceptible for mistakes even after the occurrence of habituation, and will therefore facilitate the early diagnosis of neuropathy and other disorders that affect the autonomic nerve fibers. The fast waves can also be used to detect a neuropathy in any part of the mammalian body.
The fast waves can be further used in an alternative microneurographic measurement method. Microneurography or intraneural recording is an invasive technique, which is used to assess sympathetic activity. For such a measurement a needle microelectrode is inserted directly into a nerve.
It is therefore an object of this invention to use a non-invasive method to measure fast waves of the skin potentials and any other electrophysiological signals.
It is also an object of this invention to determine autonomic conduction velocity presented by fast wave recordings to evaluate the autonomic nerve system""s function.
It is further object of this invention to provide an early and accurate diagnostic test for many diseases of autonomic dysfunction.
The objects set forth above as well as further and other objects and advantages of the present invention are achieved by the embodiments of the invention described hereinbelow.
The present invention relates to an apparatus and methods to measure any type of electrophysiological signals and especially the measurement of skin potentials characterized by low frequency oscillations and high frequency oscillations. These types of skin potentials are called slow waves and fast waves respectively. As xe2x80x9cnormalxe2x80x9d skin potentials the slow waves and fast waves are suggested to be generated by and to be under control of the ANS.
The slow waves can be detected preferably with a DC amplifier means. The xe2x80x9cnormalxe2x80x9d skin potentials are superimposed on the slow waves. The slow waves can be detected preferably with the high pass filter switched off and the low pass filter set at 0.01 Hz. The observed wavelengths with these filter settings may range between 24 hours and 2 minutes, whereas the amplitudes may vary between 100_V and 5 mV in rest recordings. The amplitude may change with values up to 25 mV upon stimulation. We suggest that these slow waves reflect cycles in metabolism and ANS and most likely sympathetic activity.
The fast waves can be measured with a sensitive DC amplifier means, but are more preferably measured with a sensitive AC amplifier means. In order to detect the fast waves, the band pass of the filters need to be set at 0.1-40 Hz, preferably the band pass is set at 0.5-30 Hz and more preferably the band pass is set at 1-10 Hz, The frequencies of the observed fast waves may range between 2-15 Hz, but frequencies higher than 15 Hz do also exist. The amplitudes of the fast waves may range between 2 and 200_V. These fast waves are generated by and under the control of ANS activity, particularly by parasympathetic activity. The fast waves are not only present in the spectrum of skin potentials, but they can be present in any electrophysiological signal that is recorded superficially or with a needle electrode inserted in any organ or tissue of a mammal""s body. The slow and fast waves possibly reflect the tone of the ANS.
The following analysis method may be used in a preferred embodiment for the fast waves, and the existing signal: 
The letters refer to amplitudes in either _V or mV at the maximum respectively and minimum, whereas the figures refer to the time periods in either milliseconds or seconds. The Roman figures refer to the area under the curve of each of the four segments. Now we will call the quotient: [A/1] the negative reactivity index and the quotient: [A/2] the negative recovery index of the wave. The quotients [B/3] and [B/4] will be the curve""s positive reactivity and positive recovery indices respectively. We further suggest to define the time segments 1+2 as _a; the time, segments 3+4 as the whole period (1+2+3+4) as _, which is a commonly used symbol for the wavelength.
From a selected portion of the measured values, all the described parameters are averaged and for each index (negative and positive reactivity, negative and positive recovery, _a, _b, _and area) its relative occurrence in a selected part of the measured values is calculated. Healthy organisms will have indices within a certain range whereas organisms with a dysfunctional ANS will have indices that deviate from the indices range of healthy ones.
In addition to the measurement of skin potentials, the apparatus is further adapted to measure any other in practice known electrophysiological signal like but not limited to the electrocardiogram, the electro-encephalogram, the electrogastrogram, and the electro-oculogram. Further, the apparatus is equipped with means to measure any in practice known physiological signal like, but not limited to: blood-pressure, oxygen saturation, plethysmography, and respiration.
The present invention relates to the simultaneous measurement of a variety of electrophysiological parameters but not limited to: the electrovegetogram extended with the analysis of fast and slow waves, the electrocardiogram (heart rate and heart rate variability), the electrogastrogram (gastric rate, variability of the gastric rate and variability of the amplitude). Optionally as part of the EAG measurement, the evaluation of fast and/or slow, waves of electrophysiological signals other than the skin potentials may be included. In addition to parameters obtained from electrophysiological signals, also minimal one parameter from physiological measurements is being evaluated. The physiological parameter being chosen from, but is not limited to the following group: respiration rate and variability in respiration rate and respiration amplitude, blood pressure variability, oxygen saturation variability, variability in plethysmogram. The influence of sensory stimuli chosen from and not limited to the following group: sound, electric, magnetism, vibration, olfaction, taste, light and pressure on the measured electro- and non- electrophysiological signals are evaluated as well. The results obtained from an EAG recording with and without the application of sensory stimuli to the organism under investigation i.e. a human being or any other mammal will provide the investigator in just one test with information about the status of the ANS of his patient. The information includes the following: the autonomic control of the cardiac and blood vessels functioning, obtained from the blood pressure and/or saturation measurements as well as from evaluation of the heart rate variability in rest and during the application of external stimuli as those generated by stimuli generator and internal stimuli generated by for instance the Valsalva maneuver, deep breathing, stop breathing and mental stress. The autonomic functioning of the stomach is obtained from the evaluation of the electrogastrogram. The analysis of the respiration frequency and variability of respiration frequency and amplitude in rest and during stimuli provide the investigator with information about the central regulation of the lung function, central and/or peripheral ANS functioning is determined with the analysis of the simultaneous skin potential recording from both hands and feet. Due to the integration of many parameters in one test, the disclosed diagnostic method will therefore be an welcome alternative to the existing methods, which are based on separate standard tests that are used for the diagnosis of ANS related disorders.
The apparatus comprises separate AC and DC amplifier modules or AC/DC amplifier modules, whereof the AC and DC amplifier modules have a minimum sensitivity of 72 nV. The AC/DC amplifier recorders are constructed to minimize electric interference between the separate AC and the DC amplifier modules. The amplifier modules are constructed to minimize cross interference between the modules. The underlying reason for the use of separate modules is to minimize the amount of noise coming from the amplifier module and/or from the external environment. This noise may obscure relevant information of the measured signal, which in turn may complicate the interpretation and analysis of the measured signal. The highest acceptable noise is 2_Vpp when electrodes are connected to the input
The disclosed apparatus can be (when preferred) extended with additional amplifier modules. For example, an apparatus comprising of four AC amplifier modules may be supplemented with for instance six AC/DC amplifier modules.
Optionally, the apparatus is equipped to detect and warn the operator for extra noise sources and bad connections prior to and during operation of the apparatus.
According to the invention, the apparatus comprises at least one amplifier module. Preferably the apparatus comprises of at least 8 amplifier modules and most preferably the apparatus comprises of at least 16 amplifier modules.
The disclosed apparatus comprises of at least one auxiliary input means for measurement of non-electrophysiological signals. Preferably the apparatus comprises of at least four auxiliary input means and most preferably it comprises of at least six auxiliary input means.
The apparatus according to the present invention comprises a stimulus generator. The stimulus generator is adapted to produce one or more external stimuli chosen from but not limited to following group: sound, electricity, magnetism, light, pressure, olfaction, taste, and vibration. The generator is adapted to produce adjustable stimuli strengths and sequences and the generator is further adapted to be operated manually as well as automatically. The generator means being fully isolated from the amplifier modules to prevent signal distortion and to maintain a low noise level.
In the present invention, the apparatus is associated with a computer means for data acquisition, data processing and control. Further the computer means controls the set up of the apparatus and comprises software filters for the signals coming from the amplifier modules. In a preferred embodiment the computer means is fully integrated with the disclosed apparatus.
The measured values may be processed by any suitable analyzing techniques known in practice such as, but not limited to: the above described method for the analysis of fast waves and skin potentials, wave-form analysis, statistical analysis, correlation techniques, fast Fourier, and Fourier analysis.
The measured values may be subject to any mathematical operation and the result of a mathematical operation being visible. For example, the software of the disclosed apparatus is adapted to subtract the skin potential signal and the EGG signal from the ECG and is adapted to display the result of these subtractions.
Additionally in selected parts of the measured signal, the relative occurrence (in percentage) of any other parameter of interest may be calculated. For example, the amplitude at each maximum in selected parts of the measured signal is the parameter of interest now, the occurrence of the same amplitude value in the selected parts is presented in percentage.
Other objects, features and advantages will be apparent from the following detailed description of preferred embodiments taken in conjunction with the accompanying drawings in which: